An important part of the continuing improvement of cardiac surgery has been the progress made in myocardial protection during cardiopulmonary bypass. Nevertheless, the consequences of myocardial ischemia during surgery remain a significant problem. The objective of this proposal is to better define the biochemical nature of the changes which convert a reversible myocardial insult to irreversible damage. We plan to investigate the hypothesis that an early relatively irreversible consequence of ischemia is loss of ATP precursors by the active catabolism of AMP and adenosine (Ad) by the myocardial cell. The breakdown of AMP to Ad or inosine monophosphate (IMP) and subsequent catabolism to inosine and hypoxanthine may prevent recovery of ATP levels when blood flow is reestablished. If AMP and Ad catabolism is an important consequence of ischemia, the way is opened for potentially effective therapy. Certain of these catabolic enzymes can be inhibited, and prevention of the breakdown of ATP precursors may be a valuable way to delay the irreversible consequences of ischemia. We believe that a satisfactory investigation of this hypothesis, however, must not only document the changes in Ad metabolism during myocardial ischemia and recovery, but it must also assess coronary blood flow and myocardial contractility. The biochemical changes are not isolated; they may both be dependent on and influence these physiological functions.